Miguel A. Checa

Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis

OBJECTIVE To examine the available evidence to assess if cryopreservation of all embryos and subsequent frozen embryo transfer (FET) results in better outcomes compared with fresh transfer. DESIGN Systematic review and meta-analysis. SETTING Centers for reproductive care. PATIENT(S) Infertility patient(s). INTERVENTION(S) An exhaustive electronic literature search in MEDLINE, EMBASE, and the Cochrane Library was performed through December 2011. We included randomized clinical trials comparing outcomes of IVF cycles between fresh and frozen embryo transfers. MAIN OUTCOME MEASURE(S) The outcomes of interest were ongoing pregnancy rate, clinical pregnancy rate, and miscarriage. RESULT(S) We included three trials accounting for 633 cycles in women aged 27-33 years. Data analysis showed that FET resulted in significantly higher ongoing pregnancy rates and clinical pregnancy rates. CONCLUSION(S) Our results suggest that there is evidence that IVF outcomes may be improved by performing FET compared with fresh embryo transfer. This could be explained by a better embryo-endometrium synchrony achieved with endometrium preparation cycles.

Use of letrozole in assisted reproduction: a systematic review and meta-analysis

BACKGROUND Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis. METHODS A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled. RESULTS Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66–2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73–2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70–2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78−1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67–2.91). CONCLUSIONS Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction.

IVF/ICSI with or without preimplantation genetic screening for aneuploidy in couples without genetic disorders: a systematic review and meta-analysis

PurposeTo assess the efficacy of preimplantation genetic screening to increase ongoing pregnancy rates in couples without known genetic disorders.MethodsSystematic review and meta-analysis of randomized controlled trials. Two reviewers independently determined study eligibility and extracted data.ResultsTen randomized trials (1,512 women) were included. The quality of evidence was moderate. Meta-analyses using a random-effects model suggest that PGS has a lower rate of ongoing pregnancies (risk ratio=0.73, 95% confidence interval 0.62–0.87) and a lower rate of live births (risk ratio=0.76, 95% confidence interval 0.64–0.91) than standard in vitro fertilization/intracytoplasmic sperm injection.ConclusionsIn women with poor prognosis or in general in vitro fertilization program, in vitro fertilization/intracytoplasmic sperm injection with preimplantation genetic screening for aneuploidy does not increase but instead was associated with lower rates of ongoing pregnancies and live births. The use of preimplantation genetic screening in daily practice does not appear to be justified.

Effects of transdermal testosterone in poor responders undergoing IVF: systematic review and meta-analysis

A systematic review and meta-analysis was performed to evaluate the effect of transdermal testosterone preceding ovarian stimulation in women with poor ovarian response undergoing IVF. Studies comparing pretreatment with transdermal testosterone versus standard ovarian stimulation among poor responders were included. The main outcome assessed was live birth. Three trials were included (113 women in the testosterone group, 112 in the control group). Testosterone-treated women achieved significantly higher live birth rate (risk ratio, RR, 1.91, 95% CI 1.01 to 3.63), clinical pregnancy rate (RR 2.07, 95% CI 1.13 to 3.78) and required significantly lower doses of FSH (RR -461.96, 95% CI -611.82 to -312.09). However, differences observed in clinical pregnancy per embryo transferred were not statistically significant (RR 1.72, 95% CI 0.91 to 3.26). No differences were observed regarding number and quality of the oocytes retrieved. In conclusion, transdermal testosterone significantly increases live birth and reduces the doses of FSH required. These findings support the theoretical synergistic role of androgens and FSH on folliculogenesis. The present data should be interpreted with caution because of the small number of trials and clinical heterogeneity. The identification of poor responders that could especially benefit from testosterone treatment should be addressed in further studies. The poor response to ovarian stimulation among women undergoing IVF is of great concern in reproductive medicine. Certain modalities have been tested to improve this response to gonadotrophin stimulation, although results from some studies have shown conflicting results. Hence, a systematic review and meta-analysis was performed in order to evaluate the effect of transdermal testosterone prior to ovarian stimulation among these women with poor ovarian response. The main outcome assessed was live birth rate. In all, three trials were included, which comprehended 113 women in the testosterone group and 112 in the control group. Women that were pretreated with transdermal testosterone achieved significantly higher live birth rate and clinical pregnancy rate and required significantly lower doses of exogenous FSH as compared with controls. However, when clinical pregnancy rate was adjusted per embryo transferred differences observed were not statistically significant. No differences were observed in the number and quality of the oocytes retrieved. In conclusion, transdermal testosterone prior to ovarian stimulation significantly increases live birth and reduces the doses of FSH required among poor responders. In addition, the identification of poor responders that could especially benefit from testosterone treatment should be addressed in further studies.

Diagnostic value of sperm DNA fragmentation and sperm high-magnification for predicting outcome of assisted reproduction treatment.

Over the last years, major improvements in the field of male infertility diagnosis have been achieved. The aim of this study was to determine the diagnostic usefulness of sperm DNA integrity and sperm vacuolisation for predicting outcome in infertile couples undergoing in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) treatments. A cohort study from 152 infertile couples undergoing sperm DNA fragmentation and high-magnification tests prior to an assisted reproduction treatment was designed. We found that the most predictive cutoff for pregnancy was 25.5% of DNA fragmentation with a negative predictive value of 72.7% (P=0.02). For the degree of vacuolisation, the best predictor of pregnancy was 73.5% of vacuolated sperm grades III+IV with a negative predictive value of 39.4% (P=0.09), which was not statistically significant. In conclusion, sperm DNA fragmentation greater than 25.5% could be associated with higher probability of failure IVF treatment. Regarding the results of the sperm analysis at high magnification, they do not allow us to predict whether or not patients will become pregnant.

Treatment of endometrial hyperplasia without atypia in peri- and postmenopausal women with a levonorgestrel intrauterine device.

Objective: To assess the effectiveness of the Mirena levonorgestrel-releasing intrauterine system (LNG-IUS) in peri- and postmenopausal women with endometrial hyperplasia without atypia. Design: All consecutive women with histologically documented endometrial hyperplasia without atypia recruited during a 1-year period participated in an open, prospective, single-center study. They were followed for at least 2 years after levonorgestrel-releasing intrauterine system insertion. The pattern of uterine bleeding was evaluated on a 4-point qualitative scale (1 = amenorrhea, 2 = scarce, 3 = normal, 4 = abundant). Results: The study population consisted of 15 women with a mean (SD) age of 49 (2.7) years. Compared with baseline, bleeding decreased quantitatively from a mean score of 3 at baseline (normal bleeding) to 2 (scarce) at 3and 6 months, and 1 (amenorrhea) at 24 months. Endometrial biopsies performed at 12 months revealed atrophicendometrium in 14 women (93.3%) and secretory endometrium in 1 (6.7%) (P < 0.001). At 24 months, endometrial atrophy was documented in 100% of women. Conclusions: The levonorgestrel-releasing intrauterine system seems to be an effective and safe alternative in the treatment of peri- and postmenopausal women with (simple) endometrial hyperplasia without atypia.

Current trends in the treatment of polycystic ovary syndrome with desire for children

Polycystic ovary syndrome (PCOS), one of the most frequent endocrine diseases, affects approximately 5%–10% of women of childbearing age and constitutes the most common cause of female sterility regardless of the need or not for treatment, a change in lifestyle is essential for the treatment to work and ovulation to be restored. Obesity is the principal reason for modifying lifestyle since its reduction improves ovulation and the capacity for pregnancy and lowers the risk of miscarriage and later complications that may occur during pregnancy (gestational diabetes, pre-eclampsia, etc). When lifestyle modification is not sufficient, the first step in ovulation induction is clomiphene citrate. The second-step recommendation is either exogenous gonadotrophins or laparoscopic ovarian surgery. Recommended third-line treatment is in vitro fertilization. Metformin use in PCOS should be restricted to women with glucose intolerance.

The impact of donor insemination on the risk of preeclampsia: a systematic review and meta-analysis

A systematic review and meta-analysis were performed to evaluate whether women who conceive with donor sperm have an increased risk of preeclampsia compared with those who use their partners sperm. Studies that compared women who were impregnated by donor and partner sperm were included. The main outcomes assessed were preeclampsia and gestational hypertension rates. Altogether, 10,898 women (2342 pregnancies by donor sperm versus 8556 by the partners sperm) were included from seven observational studies. Conception using donor sperm was associated with an increased risk of preeclampsia (odds ratio [OR] 1.63, 95% CI 1.36-1.95) compared with using a partners sperm. No difference was observed in the risk of gestational hypertension (OR 0.94, 95% CI 0.43-2.03). In conclusion, pregnancies achieved by donor sperm significantly increase the risk of preeclampsia, although the underlying mechanisms remain unclear. Additional studies are required to confirm these findings.

Changes in DNA fragmentation during sperm preparation for intracytoplasmic sperm injection over time

OBJECTIVE To compare the DNA fragmentation of semen samples established by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) after incubation in polyvinylpyrrolidone (PVP) and hyaluronic acid (HA) for different time periods. DESIGN Comparative prospective study. SETTING Center for reproductive medicine. PATIENT(S) Twenty-seven semen samples from infertile patients. INTERVENTION(S) None. METHODS Semen analysis and DNA fragmentation assays (TUNEL) were performed. Two groups were established: A) normal TUNEL (<20%); and B) Abnormal TUNEL (≥ 20%). TUNEL was performed in neat (T0), postgradient (TG), 1-hour postgradient (TG1), and 2-hour postgradient (TG2) samples and in TG2 samples after 0.5, 1.0, and 1.5 hours of incubation in PVP or HA. RESULT(S) TUNEL levels were significantly reduced after gradient separation compared with neat values. In group A, TUNEL levels were significantly higher in the TG2 + 1.5 hours in PVP and HA samples but did not reach abnormal levels. In group B, TUNEL levels were significantly higher in the TG2 + 1 hour in PVP and HA samples. CONCLUSION(S) Sperm DNA fragmentation significantly decreased after centrifugation gradient, regardless of the initial levels of the sample. Samples with TUNEL ≥ 20% were more susceptible to a significant increase in DNA fragmentation over time, with similar increases being observed over time for samples that were incubated in HA or PVP. These data may be relevant for sperm preparation for intracytoplasmic sperm injection.

Oral antioxidant treatment partly improves integrity of human sperm DNA in infertile grade I varicocele patients.

Abstract Infertile males with varicocele have the highest percentage of sperm cells with damaged DNA, compared to other infertile groups. Antioxidant treatment is known to enhance the integrity of sperm DNA; however, there are no data on the effects in varicocele patients. We thus investigated the potential benefits of antioxidant treatment specifically in grade I varicocele males. Twenty infertile patients with grade I varicocele were given multivitamins (1500 mg L-Carnitine, 60 mg vitamin C, 20 mg coenzyme Q10, 10 mg vitamin E, 200 μg vitamin B9, 1 μg vitamin B12, 10 mg zinc, 50 μg selenium) daily for three months. Semen parameters including total sperm count, concentration, progressive motility, vitality, and morphology were determined before and after treatment. In addition, sperm DNA fragmentation and the amount of highly degraded sperm cells were analyzed by Sperm Chromatin Dispersion. After treatment, patients showed an average relative reduction of 22.1% in sperm DNA fragmentation (p = 0.02) and had 31.3% fewer highly degraded sperm cells (p = 0.07). Total numbers of sperm cells were increased (p = 0.04), but other semen parameters were unaffected. These data suggest that sperm DNA integrity in grade I varicocele patients may be improved by oral antioxidant treatment.